A large variety of medical endoprostheses or implants for various applications are known from the prior art. Understood as implants within the meaning of the present invention are endovascular prostheses or other endoprostheses, for example stents, orthopedic implants such as attachment elements for bones, for example screws, plates, or pins, surgical suture material, intestinal clamps, vessel clips, prostheses for hard and soft tissue, and anchoring elements for electrodes, in particular for pacemakers or defibrillators.
Stents for the treatment of stenoses (vascular constrictions) are used particularly frequently as implants at the present time. Stents have a body in the form of an optionally perforated tubular or hollow cylindrical base lattice which is open at both longitudinal ends. The implant body of such an endoprosthesis is inserted into the vessel to be treated, and is used to support the vessel. Stents have become established in particular for the treatment of vascular diseases. Use of stents allows constricted regions in the blood vessels to be expanded, resulting in lumen gain. Although the optimal vessel cross section primarily necessary for successful treatment may be achieved by the use of stents or other implants, the permanent presence of such a foreign body initiates a cascade of microbiological processes which may lead to gradual overgrowth of the stent, and in the worst case may result in vascular occlusion. One approach to this problem is to fabricate the stent or other implants from a biodegradable material.
The term “biodegradation” refers to hydrolytic, enzymatic, and other metabolic degradation processes in the living organism which are primarily caused by the bodily fluids which come into contact with the biodegradable material of the implant, resulting in gradual disintegration of the structures of the implant containing the biodegradable material. As a result of this process, at a certain point in time the implant loses its mechanical integrity. The term “biocorrosion” is frequently used synonymously for “biodegradation.” The term “bioabsorption” includes the subsequent absorption of the degradation products by the living organism.
Suitable materials for the body of biodegradable implants may include polymer or metals, for example. The body may be composed of several of these materials. The common feature of these materials is their biodegradability. Examples of suitable polymeric compounds include polymers selected from the group including cellulose, collagen, albumin, casein, polysaccharides (PSAC), polylactide (PLA), poly-L-lactide (PLLA), polyglycol (PGA), poly-D,L-lactide-co-glycolide (PDLLA-PGA), polyhydroxybutyric acid (PHB), polyhydroxyvaleric acid (PHV), polyalkyl carbonates, polyortho esters, polyethylene terephtalate (PET), polymalonic acid (PML), polyanhydrides, polyphosphazenes, polyamino acids, and the copolymer thereof, as well as hyaluronic acid. Depending on the desired characteristics, the polymer may be present in pure form, in derivatized form, in the form of blends, or as copolymer. Metallic biodegradable materials are primarily based on alloys of magnesium and iron. The present invention preferably relates to implants whose biodegradable material of the implant body contains, at least in part, a metal, preferably iron, in particular an iron-based alloy (referred to below as “iron alloy” for short).
In the implementation of biodegradable implants, the aim is to control the degradability corresponding to the intended treatment or use of the particular implant (coronary, intracranial, renal, etc.). For many therapeutic applications, for example, it is an important target corridor for the implant to lose its integrity over a period of four weeks to six months. In this regard “integrity,” i.e., mechanical integrity, refers to the characteristic that the implant does not undergo hardly any mechanical losses compared to the nondegraded implant. This means that the implant is still mechanically stable enough to ensure that, for example, the collapse pressure drops only slightly, i.e., to a maximum of 80% of the nominal value. Thus, when integrity is present the implant is still able to fulfill its primary function of keeping the blood vessel open. Alternatively, integrity may be defined such that the implant is mechanically stable enough that in a load state in the blood vessel it undergoes minimal changes in its geometry, for example does not show appreciable collapse, i.e., under a load of at least 80% of the dilation diameter, or, in the case of a stent, has very little fracturing of supporting struts.
Implants containing an iron alloy, in particular iron-containing stents, are particularly economical and easy to manufacture. For the treatment of stenoses, for example, these implants do not lose their mechanical integrity or support effect until after a comparatively long time, i.e., after a residence time of approximately two years in the treated organism. This means that for implants containing iron, the collapse pressure decreases too slowly over time for the desired applications.
Various mechanisms for controlling the degradation of implants have been described in the prior art. These mechanisms are based, for example, on inorganic and organic protective layers or a combination thereof which resist the human corrosive environment and the corrosion processes occurring therein. Previously known approaches are characterized by the achievement of barrier layer effects which are based on spatially separating, with as few defects as possible, the corrosion medium from the metallic material. As a result, the degradation time is increased. This ensures degradation protection by use of protective layers of various compositions and by defined geometric distances (diffusion barriers) between the corrosion medium and the magnesium base material. Other approaches are based on modifying alloy components of the biodegradable material of the implant body in a targeted manner. However, the previously described approaches are usually not able to place the disintegration occurring due to the degradation process and the resulting strut fractures in the required time window. The result, in particular for implants having a body containing an iron alloy, is degradation of the implant which begins too late or which has excessive variability.